This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Most emerging infectious diseases that currently, or can potentially, cause human epidemics have evolved in other animal hosts (e.g. HIV, Influenza, West Nile Virus, Ebola), but we have little theory to translate what we know about pathogenesis, rates of pathogen evolution, immune response or epidemiology in these zoonotic diseases to behavior in human hosts. I use Metabolic Scaling Theory (MST) to address this question. MST predicts that a variety of biological rates are systematically slower in larger organisms. For example, cellular metabolism, protein synthesis and DNA replication are proportional to organism body mass, M, raised to a -1/4 power. I hypothesize that the rate at which viruses replicate in vivo and cause symptoms of disease and death are also proportional to M-1/4. Preliminary surveys of the literature suggest that the timing of pathogensis in different vertebrate hosts is consistent with MST. For example, horses and cattle take 10-15 times longer than mice to become symptomatic or to die from several viral, bacterial and prion pathogens. Additional data collection will further test the MST prediction. Immune response times may deviate from the typical 1/4 power scaling such that larger organisms initiate immune responses nearly as quickly as small organisms. Analytical equations and computer simulations of the immune system will be used to determine how particular features of the immune system may alter the scaling of immune response times, and predictions will be compared to data from the literature.